Factors impacting quality of life for breast cancer survivors.

ABSTRACT: According to the World Health Organization, breast cancer became the most common cancer in the world in 2020 and accounted for 685,000 deaths globally. In this article, breast cancer risk factors, considerations for genetic testing for BRCA1 and BRCA2 variants, signs and symptoms, and treatment are briefly discussed. Factors that impact the well-being and quality of life of women who have or have had breast cancer are also explored in depth, and practice implications for primary care providers are noted.

Top down and bottom up: A review of strategies for wellness programs in academic radiology.

Formal physician-wellness programs have come into vogue in professional organizations in recent years. Wellness programs in academic centers vary from institution to institution but foundational to all is their aim to reduce burnout and increase professional fulfillment. As radiologists in charge of wellness program implementation in different academic institutions, we describe existing academic radiology wellness programs with two detailed examples. Physician well-being programs need to be both leadership-driven (i.e., "top down") and receptive to feedback ("bottom up").

Spontaneous splenic rupture in a neonate: a case report and literature review.

Splenic rupture in a neonate is a rare but potentially fatal condition that may trigger evaluation for child abuse. It is a diagnosis of exclusion that has been reported in the surgical literature but may be underrecognized by pediatric radiologists. We report a case of a newborn with an unremarkable prenatal, delivery, and nursery course who presented with anemia, abdominal distension, and lethargy. Abdominal ultrasound with Doppler and computed tomography (CT) of the head, cervical spine, chest, abdomen, and pelvis without contrast showed findings of splenic rupture and anoxic brain injury. An extensive workup for traumatic, infectious, coagulopathic, and congenital etiologies was unrevealing, leading to a presumptive diagnosis of spontaneous splenic rupture in a neonate.

A comprehensive assessment of the prolonged febrile neutropenia evaluation in pediatric oncology patients.

BACKGROUND: Pediatric oncology patients with prolonged (≥96 hours) febrile neutropenia (absolute neutrophil count < 500/µL) often undergo an evaluation for invasive fungal disease (IFD) and other infections. Current literature suggests that beta-D-glucan (BDG), galactomannan, bronchoalveolar lavage (BAL), and computed tomography (CT) scans (sinus, chest, and abdomen/pelvis) may help determine a diagnosis in this population. METHODS: In a retrospective cohort study of all cancer/stem cell transplant patients (diagnosed 2005-2019) from one pediatric hospital, all episodes with prolonged febrile neutropenia or IFD evaluations (defined as sending a fungal biomarker or performing a CT scan to assess for infection) were identified. RESULTS: In total, 503 episodes met inclusion criteria and 64% underwent IFD evaluations. In total, 36.4% of episodes documented an infection after initiation of prolonged febrile evaluation, most commonly Clostridioides difficile colitis (6.4%) followed by a true bacterial bloodstream infection (BSI) (5.2%), proven/probable IFD (4.8%), and positive respiratory pathogen panel (3.6%). There was no difference in sinus CTs showing sinusitis (74% vs 63%, p = 0.46), whereas 32% of abdomen/pelvis CTs led to a non-IFD diagnosis, and 25% of chest CTs showed possible pneumonia. On chest CT, the positive predictive value (PPV) for IFD was 19% for nodules and 14% for tree and bud lesions. BDG had a PPV of 25% for IFD and GM 50%. BAL diagnosed IFD once and pneumocystis jirovecii pneumonia twice. CONCLUSIONS: Chest CTs and abdomen/pelvis CTs provide clinically relevant information during the prolonged febrile neutropenia evaluation, whereas BDG, galactomannan, BAL, and sinus CTs have less certain utility.

Complications of Cancer Therapy in Children: A Comprehensive Review of Neuroimaging Findings.

ABSTRACT: Complications of cancer therapy in children can result in a spectrum of neurologic toxicities that may occur at the initiation of therapy or months to years after treatment. Although childhood cancer remains rare, increasing survival rates mean that more children will be living longer after cancer treatment. Therefore, complications of cancer therapy will most likely occur with increasing frequency.At times, it is very difficult to differentiate between therapeutic complications and other entities such as tumor recurrence, development of secondary malignancy, and infection (among other conditions). Radiologists often play a key role in the diagnosis and evaluation of pediatric patients with malignancies, and thus, awareness of imaging findings of cancer complications and alternative diagnoses is essential in guiding management and avoiding misdiagnosis. The aim of this review article is to illustrate the typical neuroimaging findings of cancer therapy-related toxicities, including both early and late treatment effects, highlighting pearls that may aid in making the appropriate diagnosis.

Complications of Cancer Therapy in Children: A Comprehensive Review of Body Imaging Findings.

ABSTRACT: Complications of cancer therapy in children can result in a spectrum of toxicities that can affect any organ system and result in a range of morbidity. Complications may occur at the initiation of therapy or years following treatment. Although childhood cancer remains rare, increasing survival rates means more children are living longer following their treatment. Radiologists often play an important role in the diagnosis and evaluation of these complications, and thus, awareness of their imaging findings is essential to guide management and avoid misdiagnosis. This second part of a 2-part review aims to illustrate the typical body imaging findings of cancer therapy-related toxicities, including both early and late treatment effects. The article also discusses the differential diagnosis of imaging findings, highlighting pearls and pitfalls in making the appropriate diagnosis.

ADAD1 is required for normal translation of nuclear pore and transport protein transcripts in spermatids of Mus musculus†.

ADAD1 is a testis-specific RNA-binding protein expressed in post-meiotic spermatids whose loss leads to defective sperm and male infertility. However, the drivers of the Adad1 phenotype remain unclear. Morphological and functional analysis of Adad1 mutant sperm showed defective DNA compaction, abnormal head shaping, and reduced motility. Mutant testes demonstrated minimal transcriptome changes; however, ribosome association of many transcripts was reduced, suggesting ADAD1 may be required for their translational activation. Further, immunofluorescence of proteins encoded by select transcripts showed delayed protein accumulation. Additional analyses demonstrated impaired subcellular localization of multiple proteins, suggesting protein transport is also abnormal in Adad1 mutants. To clarify the mechanism giving rise to this, the manchette, a protein transport microtubule network, and the LINC (linker of nucleoskeleton and cytoskeleton) complex, which connects the manchette to the nuclear lamin, were assessed across spermatid development. Proteins of both displayed delayed translation and/or localization in mutant spermatids implicating ADAD1 in their regulation, even in the absence of altered ribosome association. Finally, ADAD1's impact on the NPC (nuclear pore complex), a regulator of both the manchette and the LINC complex, was examined. Reduced ribosome association of NPC encoding transcripts and reduced NPC protein abundance along with abnormal localization in Adad1 mutants confirmed ADAD1's impact on translation is required for a NPC in post-meiotic germ cells. Together, these studies lead to a model whereby ADAD1's influence on nuclear transport leads to deregulation of the LINC complex and the manchette, ultimately generating the range of physiological defects observed in the Adad1 phenotype.

Two RNA binding proteins, ADAD2 and RNF17, interact to form a heterogeneous population of novel meiotic germ cell granules with developmentally dependent organelle association.

Mammalian male germ cell differentiation relies on complex RNA biogenesis events, many of which occur in non-membrane bound organelles termed RNA germ cell granules that are rich in RNA binding proteins (RBPs). Though known to be required for male germ cell differentiation, we understand little of the relationships between the numerous granule subtypes. ADAD2, a testis specific RBP, is required for normal male fertility and forms a poorly characterized granule in meiotic germ cells. This work aimed to understand the role of ADAD2 granules in male germ cell differentiation by clearly defining their molecular composition and relationship to other granules. Biochemical analyses identified RNF17, a testis specific RBP that forms meiotic male germ cell granules, as an ADAD2-interacting protein. Phenotypic analysis of Adad2 and Rnf17 mutants identified a rare post-meiotic chromatin defect, suggesting shared biological roles. ADAD2 and RNF17 were found to be dependent on one another for granularization and together form a previously unstudied set of germ cell granules. Based on co-localization studies with well-characterized granule RBPs and organelle-specific markers, a subset of the ADAD2-RNF17 granules are found to be associated with the intermitochondrial cement and piRNA biogenesis. In contrast, a second, morphologically distinct population of ADAD2-RNF17 granules co-localized with the translation regulators NANOS1 and PUM1, along with the molecular chaperone PDI. These large granules form a unique funnel-shaped structure that displays distinct protein subdomains and is tightly associated with the endoplasmic reticulum. Developmental studies suggest the different granule populations represent different phases of a granule maturation process. Lastly, a double Adad2-Rnf17 mutant model suggests the interaction between ADAD2 and RNF17, as opposed to loss of either, is the likely driver of the Adad2 and Rnf17 mutant phenotypes. These findings shed light on the relationship between germ cell granule pools and define new genetic approaches to their study.

Prenatal Diagnosis of Skeletal Dysplasias: What Can CT Do for You?

Skeletal dysplasias (SDs) are a heterogeneous group of heritable disorders that affect development of bone and cartilage. Because each SD is individually rare and because of the heterogeneity within and among disorders, prenatal diagnosis of a specific SD remains challenging. Molecular genetic diagnosis involves invasive testing, which some patients are not amenable to. Further, genetic analysis is time consuming, and results may not become available in time to make pregnancy management decisions. Low-dose fetal CT can aid in the prenatal evaluation of SDs. The main downside is the low but true risk of fetal radiation exposure. As such, fetal CT should only be performed when there is concern for a severe skeletal dysplasia and the diagnosis is in question after a detailed ultrasound or if molecular genetic testing is unavailable and when prenatal diagnosis may affect management or counseling. Fetal CT should be obtained after consultation with geneticists, maternal-fetal medicine specialists, and fetal radiologists, and sometimes orthopedic surgeons or neonatologists. The purpose of this study was to review the technique of and indications for fetal CT, as well as discuss fetal radiation risk. Illustrative cases will demonstrate when and how CT may be helpful in the diagnosis of SDs.

Kinetic proteomics identifies targeted changes in liver metabolism and the ribo-interactome by dietary sulfur amino acid restriction.

Dietary sulfur amino acid restriction (SAAR) protects against diet-induced obesity, extends healthspan, and coincides with an overall reduction in hepatic protein synthesis. To explore the underpinnings of SAAR-induced slowed growth and its impact on liver metabolism and proteostasis, we resolved changes in hepatic mRNA and protein abundances and compared synthesis rates of individual liver proteins. To achieve this, adult male mice were provided deuterium-labeled drinking water while freely consuming either a regular-fat or high-fat diet that was SAA restricted. Livers from these mice and their respective dietary controls were used to conduct transcriptomic, proteomic, and kinetic proteomic analyses. We found that remodeling of the transcriptome by SAAR was largely agnostic to dietary fat content. Shared signatures included activation of the integrated stress response alongside alterations in metabolic processes impacting lipids, fatty acids, and amino acids. Changes to the proteome correlated poorly with the transcriptome, and yet, functional clustering of kinetic proteomic changes in the liver during SAAR revealed that the management of fatty acids and amino acids were altered to support central metabolism and redox balance. Dietary SAAR also strongly influenced the synthesis rates of ribosomal proteins and ribosome-interacting proteins regardless of dietary fat. Taken together, dietary SAAR alters the transcriptome and proteome in the liver to safely manage increased fatty acid flux and energy use and couples this with targeted changes in the ribo-interactome to support proteostasis and slowed growth.

Perinatal intermittent hypoxia increases early susceptibility to ANG II-induced hypertension in adult male but not in female Sprague-Dawley rats.

Prenatal, perinatal, and adulthood exposure to chronic intermittent hypoxia (IH) increases blood pressure in rodents. Males exposed to chronic IH have higher blood pressure versus females. However, it is unknown if this same-sex difference exists with acute perinatal IH. We tested the hypothesis that acute perinatal IH increases baseline blood pressure and enhances sensitivity to angiotensin II (ANG II)-induced hypertension in male Sprague-Dawley rats. Male and female pups were randomized to control (room air) or IH (10 min of ∼10% O2 for 3 times/day) for the first 8 days of life. IH decreased oxygen saturation, as confirmed via a pulse oximeter. Pups were weaned at postnatal day 21. Blood pressure was measured via telemetry beginning at 14 wk of age and analyzed separately into light and dark phases to assess circadian rhythm. Osmotic minipumps to deliver ANG II were implanted at 15 wk of age. Perinatal IH exposure did not alter baseline blood pressure. One week of ANG II treatment increased blood pressure in light and dark periods in males exposed to IH versus control; there was no effect in females. Blood pressure among the groups was comparable following 2 wk of ANG II infusion. Perinatal IH did not change the circadian rhythm. Following ANG II treatment, indexes of renal injury were measured. Perinatal IH did not alter kidney size, structure, nephron number, or creatinine clearance. These data indicate that acute perinatal IH enhances early ANG II-induced hypertension in males, independent of nephron loss or decreases in body weight or kidney function.NEW & NOTEWORTHY The impact of acute intermittent hypoxia (IH) in early life on blood pressure in adulthood is unknown. This study used a new model exposing female and male rat pups to acute IH in the first 8 days of life, without exposing the dam. Although baseline blood pressure was not altered in adulthood, IH increased susceptibility to angiotensin II hypertension only in males, supporting increased susceptibility of males exposed to IH to a second cardiovascular stressor.

Modern tools applied to classic structures: Approaches for mammalian male germ cell RNA granule research.

First reported in the 1800s, germ cell granules are small nonmembrane bound RNA-rich regions of the cytoplasm. These sites of critical RNA processing and storage in the male germ cell are essential for proper differentiation and development and are present in a wide range of species from Caenorhabditis elegans through mammals. Initially characterized by light and electron microscopy, more modern techniques such as immunofluorescence and genetic models have played a major role in expanding our understanding of the composition of these structures. While these methods have given light to potential granule functions, much work remains to be done. The current expansion of imaging technologies and omics-scale analyses to germ cell granule research will drive the field forward considerably. Many of these methods, both current and upcoming, have considerable caveats and limitations that necessitate a holistic approach to the study of germ granules. By combining and balancing different techniques, the field is poised to elucidate the nature of these critical structures.

Making intussusception reductions easier: use of medical air in lieu of manual pump.

BACKGROUND: Pneumatic reduction of ileocolic intussusception is commonly performed with manual insufflators. The challenge of operating a handheld device while controlling the fluoroscope and monitoring the reduction could be obviated if the manual insufflation could be eliminated. OBJECTIVE: The aim in this retrospective study was to describe and evaluate the use of medical wall air in intussusception reduction. MATERIALS AND METHODS: We retrospectively reviewed all intussusception reductions over a period of years: from 2015 to 2018 using the manual insufflator and from 2018 to 2021 using medical air. We compared success rates, complication rates and time to reduction as documented on fluoroscopic image time stamps. Demographic data were obtained from the medical record. Attending radiologists and fluoroscopic technologists indicated their preference between methods, ease of use, perceived duration of reduction and perceived difference in success rates through an anonymous internal survey. RESULTS: There were 179 first reduction attempts in 167 patients (93 attempts during the period using the manual insufflator and 86 after converting to wall air). There was no difference in reduction duration (8:23 min for insufflation, 8:22 min for wall air, P=0.99) and no statistically significant difference in success rate (66.8% for insufflation and 79.1% for wall air, P=0.165). All survey respondents preferred the wall air method. The vast majority (93%) perceived that the wall air method was faster. CONCLUSION: Hospital wall air can be used to successfully reduce intussusceptions without incurring time burden or loss of effectiveness. The method leads to a perception of increased efficiency.